We plan to investigate the mechanisms of hyperthyroidism in Graves' disease with particular attention to possible immunopathogenesis. We will study human thyroid tissue in the form of isolated cells, membranes, membrane fragments, reaggregated cells and tissue slices. The early steps of thyroid secretion which include binding of the thyroid stimulator and ingestion of colloid have some similarity to the processes of opsonification and phagocytosis by macrophages. Therefore, methods helpful in studying phagocytosis will be emphasized. Several thyroid stimulators including LATS, HTS (human thyroid stimulator) and the effects of immune lymphocytes will be studied. We will seek to identify immunoglobulin binding sites on thyroid cells and we will study the phagocytic activity of thyroid epithelial cell preparations in vitro. We will also study the ability of thyroid lysosomes to secrete enzymes extracellularly following Cytochalasin B treatment and we will separate apical from basal and lateral plasma membranes in order to study the different functional activities of those portions of the thyroid epithelial cell.